1. Field of the Invention
This invention relates to tricyclic aminoalkylcarboxamide derivatives which selectively bind to brain dopamine receptor subtypes. It also relates to pharmaceutical compositions comprising such compounds. It further relates to the use of such compounds in the treatment or prevention of various neuropsychochological disorders as schizophrenia and other central nervous system diseases.
2. Description of the Related Art
The therapeutic effect of conventional antipsychotics, known as neuroleptics, is generally believed to be exerted through blockade of dopamine receptors. However, neuroleptics are frequently responsible for undesirable extrapyramidal side effects (EPS) and tardive dyskinesias, which are attributed to blockade of D.sub.2 receptors in the striatal region of the brain. The dopamine D.sub.3 receptor subtype has recently been identified (Sokoloff et al., Nature, 347, 146 (1990 )). Its unique localization in limbic brain areas and its differential recognition of various antipsychotics suggest that the D.sub.3 receptor plays a role in the etiology of schizophrenia. Selective D.sub.3 antagonists thus are expected to be effective antipsychotics free from the neurological side effects displayed by conventional neuroleptics.
U.S. Pat. No. 5,393,835 discloses N-aminoalkyl-2-napthalamides described to have affinity at dopamine D.sub.3 receptors.
Murray et al., Bioorg. Med. Chem. Let. 5: 219 (1995), describe 4-carboxamidobiphenyls said to have affinity at dopamine D.sub.3 receptors.
International Patent Application WO 9511903 discloses tricylic diazaphenanthrene carboxamides having affinity for 5-HT.sub.1A receptors.
European Patent Application EP 206225 A2 discloses aryl alkyl azatricyclic compounds.